Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1 (Th1) type responses which are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta2-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta2-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta2-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta2-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.

Beta 2 agonists prevent Th1 development by selective inhibition of IL-12 / P., Panina Bordignon; D., Mazzeo; P., Di Lucia; Dd, D'Ambrosio; R., Lang; Fabbri, Leonardo; C., Self; F., Sinigaglia. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 100:(1997), pp. 1513-1519.

Beta 2 agonists prevent Th1 development by selective inhibition of IL-12

FABBRI, Leonardo;
1997

Abstract

Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1 (Th1) type responses which are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta2-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta2-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta2-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta2-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.
100
1513
1519
Beta 2 agonists prevent Th1 development by selective inhibition of IL-12 / P., Panina Bordignon; D., Mazzeo; P., Di Lucia; Dd, D'Ambrosio; R., Lang; Fabbri, Leonardo; C., Self; F., Sinigaglia. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 100:(1997), pp. 1513-1519.
P., Panina Bordignon; D., Mazzeo; P., Di Lucia; Dd, D'Ambrosio; R., Lang; Fabbri, Leonardo; C., Self; F., Sinigaglia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/451437
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